1. Field of the Invention
The present invention relates to a use of 15-keto-prostaglandin compound for improvement of encephalic function.
Prostaglandins (hereinafter, prostaglandin is referred to as PG) are members of a class of organic carboxylic acid that are contained in human and most other mammalian tissues or organs and that exhibit a wide range of physiological activities. Naturally occurring PGs possess as a common structural feature the prostanoic acid skeleton: ##STR1## Some of synthetic analogues have somewhat modified skeletons. The PGs are classified based on the structural feature of five-membered ring moiety into PGAs, PGBs, PGCs, PGDs, PGEs, PGFs, PGGs, PGHs and PGJs, while PGIs have an different skeleton, shown below, formed by cyclization between the .alpha.-chain and the five-membered ring. ##STR2## These are further classified based on the presence or absence of unsaturation and oxidation in the chain moiety as:
Subscript 1 - - - 13,14-unsaturated-15-OH PA1 Subscript 2 - - - 5,6- and 13,14-diunsaturated-15-OH PA1 Subscript 3 - - - 5,6-13,14- and 17,18-triunsaturated-15-OH
Further, PGFs are sub-classified according to the configuration of hydroxy groups at 9-position into .alpha. (hydroxy group being in alpha configuration) and .beta. (hydroxy group being in beta configuration).
2. Background Information
JP-A-58-164512 discloses that 15-cycloalkyl-6-oxo-PGE.sub.1 s, 15-cycloalkyl-PGI.sub.1 s and PGI.sub.2 s, 15-cycloalkyl-6,9.alpha.-nitrilo-PGI.sub.1 s, and 15-cycloalkyl-6,9.alpha.-thio-PGI.sub.1 s and -PGI.sub.2 s have a protective effect to cell disorder including cerebral vascular disorder. JP-A-58-203911 discloses that some 6-oxo-PGE.sub.1 s and PGI.sub.1 s having one or two methyl substituents on 15,16,17 and/or 20 positions and defined 15-cyclopentyl-PGI.sub.1 s have a protective effect to cell disorder. JP-A-59-73522 discloses that some PGD.sub.2 - or PGE.sub.1 derivatives can be used as a treating agent for hypoxia of cerebral nerve cells. Further, carbacyclin (also known as 9(O)-methanoprostacyclin or 9(O)-methano-PGI.sub.2), which is a synthetic PG derivative having a methylene group in place of the oxygen at position 6a(9.alpha.) of PGI.sub.2, is known to have an action of inhibiting platelet aggregation. Also, compound having a nitrogen in place of the oxgen at position 6a(9.alpha.) and a sulfur in place of the methylene at position 5 of PGI.sub.2 (i.e. 9-deoxy-9.alpha.,6-nitrilo-5-thia-PGF.sub.1.alpha.) is known. These compounds, however, do not fall within the category of 15-keto-PGs or derivatives thereof.
EP-A-0310305 discloses that 15-keto-PGEs can be used as a cathartic.
PGEs having an oxo group at position 6 and two fluorine atoms at position 5 have also been known (JP-A-32054/1990) which have been described as compounds having actions reducing gastro-juice and preventing stress ulcer. Further, compounds having an oxo group in place of hydroxy group at position 15 and derivatives of these compounds have been known as compounds having anti-ulcer ant uterine contracting actions etc. but little intestine contracting action. While the fact that a single compound simultaneously has a plurality of actions may seem to be advantageous, it is also to be noted that in some cases the presence of actions other than those useful in confronted treatment is rather undesirable and seemed to be disadvantageous as having side-effects. Accordingly, a compounds having only the desired action are advantageous from such viewpoint.
Among various causes possible for the deterioration of cerebral function, the local disorder of cerebral vascular kinetics due to ischemic lesion, hemorrhagic lesion or edemstous hydrocephalus and the diffuse disorder due to compressive lesion may be mentioned Another cause may be the secondary disorder of encephalic metabolism.
In order to treat these disorders, two factors should be considered, i.e. improvement of the cerebral circulation and that of the basic activity of cerebral cells. Accordingly, there is a continuous need for a medicament having both the improving activity.
After an extensive study on the biological activity of 15-keto-PGs, the present inventor discovered that 15-keto-PGs have excellent encephalic metabolism activating action, encephalic function protecting action and encephalic blood circulation improving action, and therefore can be used for improvement of encephalic function.